Alkylphosphocholines are a new class of organic compounds, which exhibit diversified anti-neoplastic activities (M. Lohmeyer and R. Bittman, Antitumor Ether Lipids and Alkylphosphocholines, DOF, 19 (11), 1021-1037 (1994)). The effect of the alkylphosphocholines in this connection may be based on different, molecular and biochemical mechanisms, some of which take place on the level of the plasma membrane of the cell.
It is well known that alkylphosphocholines influence inositol metabolism, the interaction with phospholipases or inhibition of protein kinase C and thus that this class of substances has a general influence on cellular signal transduction (K. Maly et al., Interference of New Alkylphospholipid Analogues With Mitogenic Signal Transduction, Anti-Cancer Drug Design, 10, 411-425 (1995); and P. Hilgard, et al., D21266, A New Heterocyclic Alkylphospholipid with Antitumor Activity, Eur. J. Cancer, 33 (3), 442-446 (1997)). Thus, the alkylphosphocholine perifosine shows growth-inhibitory properties in relation to various melanoma, CNS, lung, colon, prostate and breast cancer cell lines with an IC50 ranging from 0.2 to 20 μM.
It is further known that perifosine blocks tumor cells in the G1-S and G2-M phase of the cell cycle (V. Patel, et al., A Novel Alkylphospholipid, Induces p. 21 Waf1 Expression in Squamous Carcinoma Cells through a p53-independent Pathway, Leading to Loss in Cyclindependent Kinase Activity and Cell Cycle Arrest, Cancer Research 62, 1401-1409 (2002)).
It is known that the use of alkylphosphocholines before or together with radiation therapy leads its synergistic effects during the treatment of tumors (P. Principe et al., Evaluation of Combinations of Antineoplastic Ether Phospholipids and Chemotherapeutic Drugs, Anti-Cancer Drugs, 3 (6), 577-587 (1992)). It has also been reported that different glycerol-3-phospholipids, such as ET-18-OOCH3, in combination with different DNA-interacting substances or tubulin binders increase the anti-tumor activity in vitro in a different tumor cell lines (P. Principe et al., Synergistic Cytotoxic Effect of Aza-alkylphospholipids in Association with Chemotherapeutic Drugs, J. Lipid Mediators Cell Signalling, 10 (1-2), 171-173 (1994)).
Despite advances in the treatment of cancer using perifosine and a variety of other antitumor agents, there still exists a need in developing more effective therapies for the treatment of a variety of different types of cancer. Certain types of cancers, such as multiple myeloma, renal cancer, breast cancer and colon cancer have proved to be particularly difficult to control. Thus, an effective means of treating these cancers that prolong the survival rate of patients without causing serious side effects would be a considerable advance.